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Severe combined immunodeficiency due to ADA deficiency

MedGen UID:
354935
Concept ID:
C1863236
Disease or Syndrome
Synonyms: ADA deficiency; ADA-SCID; Adenosine Deaminase Deficiency; Adenosine deaminase deficiency; Adenosine deaminase deficient severe combined immunodeficiency; Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease (SCID); SCID DUE TO ADA DEFICIENCY, EARLY-ONSET; Severe combined immunodeficiency due to adenosine deaminase deficiency; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
Somatic mosaicism
MedGen UID:
356183
Concept ID:
C1866227
Finding
 
Gene: ADA
Cytogenetic location: 20q13.12
OMIM®: 102700

Disease characteristics

Excerpted from the GeneReview: Adenosine Deaminase Deficiency
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months. Less severe "delayed" onset combined immune deficiency (CID), usually diagnosed between age one and ten years. "Late/adult onset" CID, diagnosed in the second to fourth decades. Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function. Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Michael Hershfield   view full author information

Additional description

From GHR
Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. Affected children also grow much more slowly than healthy children and some have developmental delay. Most individuals with ADA deficiency are diagnosed with SCID in the first 6 months of life. Without treatment, these babies usually do not survive past age 2. In about 10 percent to 15 percent of cases, onset of immune deficiency is delayed to between 6 and 24 months of age (delayed onset) or even until adulthood (late onset). Immune deficiency in these later-onset cases tends to be less severe, causing primarily recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems.  http://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency

Clinical features

Failure to thrive
MedGen UID:
776583
Concept ID:
C2364119
Finding
B-cell lymphoma
MedGen UID:
506689
Concept ID:
CN167917
Finding
A type of lymphoma that originates in B-cells.
Diffuse mesangial sclerosis
MedGen UID:
350863
Concept ID:
C1863240
Finding
Sinusitis
MedGen UID:
504406
Concept ID:
CN000238
Finding
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Anterior rib cupping
MedGen UID:
337520
Concept ID:
C1846154
Finding
Platyspondyly
MedGen UID:
355353
Concept ID:
C1865023
Finding
Sinusitis
MedGen UID:
504406
Concept ID:
CN000238
Finding
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Abnormality of pelvic girdle bone morphology
MedGen UID:
428305
Concept ID:
CN002405
Finding
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diarrhea
MedGen UID:
368098
Concept ID:
C1963091
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Increased IgE level
MedGen UID:
374150
Concept ID:
C1839165
Finding
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
Absent specific antibody response
MedGen UID:
354937
Concept ID:
C1863246
Finding
Severe B lymphocytopenia
MedGen UID:
350238
Concept ID:
C1863715
Finding
Lymphopenia
MedGen UID:
409568
Concept ID:
C1963164
Finding
Eosinophilia
MedGen UID:
412195
Concept ID:
C2240374
Finding
A condition in which the number of eosinophils (a type of white blood cell) in the blood is greatly increased. Eosinophilia is often a response to infection or allergens (substances that cause an allergic response).
Autoimmune hemolytic anemia
MedGen UID:
504990
Concept ID:
CN001709
Finding
An autoimmune form of hemolytic anemia.
Autoimmune thrombocytopenia
MedGen UID:
500917
Concept ID:
CN001785
Finding
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
B-cell lymphoma
MedGen UID:
506689
Concept ID:
CN167917
Finding
A type of lymphoma that originates in B-cells.
Increased IgE level
MedGen UID:
374150
Concept ID:
C1839165
Finding
Absent specific antibody response
MedGen UID:
354937
Concept ID:
C1863246
Finding
Pneumonia
MedGen UID:
505095
Concept ID:
CN001891
Finding
Inflammation of any part of the lung parenchyma.
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased IgE level
MedGen UID:
374150
Concept ID:
C1839165
Finding
Recurrent fungal infections
MedGen UID:
336166
Concept ID:
C1844384
Finding
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
Absent specific antibody response
MedGen UID:
354937
Concept ID:
C1863246
Finding
Severe B lymphocytopenia
MedGen UID:
350238
Concept ID:
C1863715
Finding
Lymphopenia
MedGen UID:
409568
Concept ID:
C1963164
Finding
Eosinophilia
MedGen UID:
412195
Concept ID:
C2240374
Finding
A condition in which the number of eosinophils (a type of white blood cell) in the blood is greatly increased. Eosinophilia is often a response to infection or allergens (substances that cause an allergic response).
Recurrent bacterial infections
MedGen UID:
411712
Concept ID:
C2748958
Finding
Autoimmune hemolytic anemia
MedGen UID:
504990
Concept ID:
CN001709
Finding
An autoimmune form of hemolytic anemia.
Autoimmune thrombocytopenia
MedGen UID:
500917
Concept ID:
CN001785
Finding
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Severe combined immunodeficiency
MedGen UID:
505637
Concept ID:
CN003925
Finding
Severe combine immunodeficiency (SCID) is a primary immune deficiency that is characterized by a severe defect in both the T- and B-lymphocyte systems.
Aplasia of the thymus
MedGen UID:
505801
Concept ID:
CN004758
Finding
Absence of the thymus.

Term Hierarchy

Recent clinical studies

Etiology

Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K, Hönig M, Friedrich W, Gennery A, Slatter M, Bredius R, Finocchi A, Cancrini C, Aiuti A, Porta F, Lanfranchi A, Ridella M, Steward C, Filipovich A, Marsh R, Bordon V, Al-Muhsen S, Al-Mousa H, Alsum Z, Al-Dhekri H, Al Ghonaium A, Speckmann C, Fischer A, Mahlaoui N, Nichols KE, Grunebaum E, Al Zahrani D, Roifman CM, Boelens J, Davies EG, Cavazzana-Calvo M, Notarangelo L, Gaspar HB; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and European Society for Immunodeficiency
Blood 2012 Oct 25;120(17):3615-24; quiz 3626. Epub 2012 Jul 12 doi: 10.1182/blood-2011-12-396879. [Epub ahead of print] PMID: 22791287
Hussain W, Batool A, Ahmed TA, Bashir MM
J Pak Med Assoc 2012 Mar;62(3):297-9. PMID: 22764473
Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, Avcin T, Qasim W, Davies EG, Niehues T, Ehl S
Clin Immunol 2011 Oct;141(1):73-82. Epub 2011 May 30 doi: 10.1016/j.clim.2011.05.007. [Epub ahead of print] PMID: 21664875
Kühl JS, Schwarz K, Münch A, Schmugge M, Pekrun A, Meisel C, Wahn V, Ebell W, von Bernuth H
Klin Padiatr 2011 Mar;223(2):85-9. Epub 2011 Jan 26 doi: 10.1055/s-0030-1269916. [Epub ahead of print] PMID: 21271505
Silver JN, Elder M, Conlon T, Cruz P, Wright AJ, Srivastava A, Flotte TR
Hum Gene Ther 2011 Aug;22(8):935-49. Epub 2011 Mar 13 doi: 10.1089/hum.2010.121. [Epub ahead of print] PMID: 21142972

Diagnosis

Manson D, Diamond L, Oudjhane K, Hussain FB, Roifman C, Grunebaum E
Pediatr Radiol 2013 Mar;43(5):589-92. Epub 2012 Nov 24 doi: 10.1007/s00247-012-2564-2. [Epub ahead of print] PMID: 23179487
Hussain W, Batool A, Ahmed TA, Bashir MM
J Pak Med Assoc 2012 Mar;62(3):297-9. PMID: 22764473
Booth C, Algar VE, Xu-Bayford J, Fairbanks L, Owens C, Gaspar HB
J Clin Immunol 2012 Jun;32(3):449-53. Epub 2012 Feb 21 doi: 10.1007/s10875-012-9658-3. [Epub ahead of print] PMID: 22350222
Azzari C, la Marca G, Resti M
J Allergy Clin Immunol 2011 Jun;127(6):1394-9. doi: 10.1016/j.jaci.2011.03.040. PMID: 21624616
Kühl JS, Schwarz K, Münch A, Schmugge M, Pekrun A, Meisel C, Wahn V, Ebell W, von Bernuth H
Klin Padiatr 2011 Mar;223(2):85-9. Epub 2011 Jan 26 doi: 10.1055/s-0030-1269916. [Epub ahead of print] PMID: 21271505

Therapy

Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K, Hönig M, Friedrich W, Gennery A, Slatter M, Bredius R, Finocchi A, Cancrini C, Aiuti A, Porta F, Lanfranchi A, Ridella M, Steward C, Filipovich A, Marsh R, Bordon V, Al-Muhsen S, Al-Mousa H, Alsum Z, Al-Dhekri H, Al Ghonaium A, Speckmann C, Fischer A, Mahlaoui N, Nichols KE, Grunebaum E, Al Zahrani D, Roifman CM, Boelens J, Davies EG, Cavazzana-Calvo M, Notarangelo L, Gaspar HB; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and European Society for Immunodeficiency
Blood 2012 Oct 25;120(17):3615-24; quiz 3626. Epub 2012 Jul 12 doi: 10.1182/blood-2011-12-396879. [Epub ahead of print] PMID: 22791287
Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M
Methods Enzymol 2012;507:15-27. doi: 10.1016/B978-0-12-386509-0.00002-8. PMID: 22365767
Booth C, Algar VE, Xu-Bayford J, Fairbanks L, Owens C, Gaspar HB
J Clin Immunol 2012 Jun;32(3):449-53. Epub 2012 Feb 21 doi: 10.1007/s10875-012-9658-3. [Epub ahead of print] PMID: 22350222
Montiel-Equihua CA, Thrasher AJ, Gaspar HB
Curr Gene Ther 2012 Feb 1;12(1):57-65. PMID: 22348551
Gaspar HB, Cooray S, Gilmour KC, Parsley KL, Zhang F, Adams S, Bjorkegren E, Bayford J, Brown L, Davies EG, Veys P, Fairbanks L, Bordon V, Petropoulou T, Kinnon C, Thrasher AJ
Sci Transl Med 2011 Aug 24;3(97):97ra80. doi: 10.1126/scitranslmed.3002716. PMID: 21865538

Prognosis

Michos A, Tzanoudaki M, Villa A, Giliani S, Chrousos G, Kanariou M
J Clin Immunol 2011 Oct;31(5):778-83. Epub 2011 Jul 6 doi: 10.1007/s10875-011-9564-0. [Epub ahead of print] PMID: 21732012
Moncada-Vélez M, Vélez-Ortega A, Orrego J, Santisteban I, Jagadeesh J, Olivares M, Olaya N, Hershfield M, Candotti F, Franco J
Scand J Immunol 2011 Nov;74(5):471-81. doi: 10.1111/j.1365-3083.2011.02593.x. PMID: 21671975Free PMC Article
Kühl JS, Schwarz K, Münch A, Schmugge M, Pekrun A, Meisel C, Wahn V, Ebell W, von Bernuth H
Klin Padiatr 2011 Mar;223(2):85-9. Epub 2011 Jan 26 doi: 10.1055/s-0030-1269916. [Epub ahead of print] PMID: 21271505
Tezcan I, Ersoy F, Cağlar M, Sanal O, Kotiloğlu E, Aysun S
Turk J Pediatr 1995 Oct-Dec;37(4):383-9. PMID: 8560606
Hirschhorn R, Chakravarti V, Puck J, Douglas SD
Am J Hum Genet 1991 Oct;49(4):878-85. PMID: 1680289Free PMC Article

Clinical prediction guides

Grunebaum E, Cohen A, Roifman CM
Curr Opin Allergy Clin Immunol 2013 Dec;13(6):630-8. doi: 10.1097/ACI.0000000000000006. PMID: 24113229
Candotti F, Shaw KL, Muul L, Carbonaro D, Sokolic R, Choi C, Schurman SH, Garabedian E, Kesserwan C, Jagadeesh GJ, Fu PY, Gschweng E, Cooper A, Tisdale JF, Weinberg KI, Crooks GM, Kapoor N, Shah A, Abdel-Azim H, Yu XJ, Smogorzewska M, Wayne AS, Rosenblatt HM, Davis CM, Hanson C, Rishi RG, Wang X, Gjertson D, Yang OO, Balamurugan A, Bauer G, Ireland JA, Engel BC, Podsakoff GM, Hershfield MS, Blaese RM, Parkman R, Kohn DB
Blood 2012 Nov 1;120(18):3635-46. Epub 2012 Sep 11 doi: 10.1182/blood-2012-02-400937. [Epub ahead of print] PMID: 22968453Free PMC Article
Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K, Hönig M, Friedrich W, Gennery A, Slatter M, Bredius R, Finocchi A, Cancrini C, Aiuti A, Porta F, Lanfranchi A, Ridella M, Steward C, Filipovich A, Marsh R, Bordon V, Al-Muhsen S, Al-Mousa H, Alsum Z, Al-Dhekri H, Al Ghonaium A, Speckmann C, Fischer A, Mahlaoui N, Nichols KE, Grunebaum E, Al Zahrani D, Roifman CM, Boelens J, Davies EG, Cavazzana-Calvo M, Notarangelo L, Gaspar HB; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and European Society for Immunodeficiency
Blood 2012 Oct 25;120(17):3615-24; quiz 3626. Epub 2012 Jul 12 doi: 10.1182/blood-2011-12-396879. [Epub ahead of print] PMID: 22791287
Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M
Methods Enzymol 2012;507:15-27. doi: 10.1016/B978-0-12-386509-0.00002-8. PMID: 22365767
Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, Avcin T, Qasim W, Davies EG, Niehues T, Ehl S
Clin Immunol 2011 Oct;141(1):73-82. Epub 2011 May 30 doi: 10.1016/j.clim.2011.05.007. [Epub ahead of print] PMID: 21664875

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